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  IL-6/Stat3-Dependent Induction of a Distinct, Obesity-Associated NK Cell Subpopulation Deteriorates Energy and Glucose Homeostasis

Theurich, S., Tsaousidou, E., Hanssen, R., Lempradl, A. M., Mauer, J., Timper, K., et al. (2017). IL-6/Stat3-Dependent Induction of a Distinct, Obesity-Associated NK Cell Subpopulation Deteriorates Energy and Glucose Homeostasis. Cell Metab, 26(1), 171-184 e6. doi:10.1016/j.cmet.2017.05.018.

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Item Permalink: https://hdl.handle.net/21.11116/0000-0001-5938-D Version Permalink: https://hdl.handle.net/21.11116/0000-0001-5939-C
Genre: Journal Article

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https://www.ncbi.nlm.nih.gov/pubmed/28683285 (Any fulltext)
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 Creators:
Theurich, S.1, Author
Tsaousidou, E.1, Author
Hanssen, R.1, Author
Lempradl, A. M.1, Author
Mauer, J.1, Author
Timper, K.1, Author
Schilbach, K.1, Author
Folz-Donahue, K.1, Author
Heilinger, C.1, Author
Sexl, V.1, Author
Pospisilik, J. A.1, Author
Wunderlich, F. T.1, Author
Bruning, J. C.1, Author
Affiliations:
1Max Planck Institute for Biology of Ageing, Max Planck Society, Joseph-Stelzmann-Str. 9b, D-50931 Cologne, DE, ou_1942284              

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Free keywords: Csf1r IL-6 receptor IL6Ra Stat3 diabetes metaflammation myeloid gene signature natural killer cells obesity obesity-associated inflammation
 Abstract: Natural killer (NK) cells contribute to the development of obesity-associated insulin resistance. We demonstrate that in mice obesity promotes expansion of a distinct, interleukin-6 receptor (IL6R)a-expressing NK subpopulation, which also expresses a number of other myeloid lineage genes such as the colony-stimulating factor 1 receptor (Csf1r). Selective ablation of this Csf1r-expressing NK cell population prevents obesity and insulin resistance. Moreover, conditional inactivation of IL6Ra or Stat3 in NK cells limits obesity-associated formation of these myeloid signature NK cells, protecting from obesity, insulin resistance, and obesity-associated inflammation. Also in humans IL6Ra+ NK cells increase in obesity and correlate with markers of systemic low-grade inflammation, and their gene expression profile overlaps with characteristic gene sets of NK cells in obese mice. Collectively, we demonstrate that obesity-associated inflammation and metabolic disturbances depend on interleukin-6/Stat3-dependent formation of a distinct NK population, which may provide a target for the treatment of obesity, metaflammation-associated pathologies, and diabetes.

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 Dates: 2017
 Publication Status: Issued
 Pages: -
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 Rev. Type: -
 Identifiers: Other: 28683285
DOI: 10.1016/j.cmet.2017.05.018
ISSN: 1932-7420 (Electronic)1550-4131 (Linking)
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Title: Cell Metab
Source Genre: Journal
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Pages: - Volume / Issue: 26 (1) Sequence Number: - Start / End Page: 171 - 184 e6 Identifier: -